Andrew D. Bowser

Compared with placebo, opioids provide very modest improvements in chronic noncancer pain and physical functioning that decrease over time, according to the authors of a systematic review and meta-analysis of nearly 100 randomized clinical trials.

There was little difference in pain control between opioids and nonopioid alternatives such as NSAIDs in a subset of nine such comparative trials, reported the authors, led by Jason W. Busse, DC, PhD, of the department of anesthesia at McMaster University, Hamilton, Ont.

Pain benefits of opioids decreased over time in longer trials, possibly because of opioid tolerance or hyperalgesia, a condition marked by hypersensitivity to pain. “A reduced association with benefit over time might lead to prescription of higher opioid doses and consequent harms,” Dr. Busse and his coauthors wrote in JAMA.

The meta-analysis included 96 randomized clinical trials including 26,169 patients with chronic noncancer pain.

Opioid treatment did significantly improve pain and physical function versus placebo, though the magnitude of benefit was small, according to the investigators. The reduction in pain was –0.69 cm on a 10-cm visual analog scale (P less than .001), based on high-quality evidence from 42 randomized, controlled trials that followed patients for at least 3 months.

The improvement in physical functioning was likewise significant but small at 2.04 out of 100 points on the SF-36 physical component score (P less than .001). Emotional and role functioning were not significantly improved by opioid use.

Opioid use was linked to increased vomiting incidence versus placebo, with a relative risk of 4.12 (95% CI, 3.34-5.07; P less than .001) for patients in “nonenrichment” trials – those studies that included all patients regardless of whether or not they reported lack of improvement or had substantial adverse events during a study run-in period.

Nausea, constipation, dizziness, drowsiness, pruritus, and dry mouth were also linked to opioid use as compared with placebo, Dr. Busse and his colleagues reported.

The benefit of opioids and nonopioid alternatives appeared to be similar in this meta-analysis, though the available evidence from comparative studies was of low to moderate quality, the authors advised.

In moderate-quality evidence from nine clinical trials of opioids versus NSAIDs including 1,431 patients, there was no difference in pain relief between the two interventions, the investigators said. Moreover, comparisons of physician functioning also suggested no difference, while opioids were associated with more vomiting.

Both tricyclic antidepressants and synthetic cannabinoids offered similar pain relief, compared with opioids, based on low-quality clinical trial evidence, they added, while moderate-quality evidence suggested opioids offered superior pain relief, compared with anticonvulsants.

Support for the study came from the Canadian Institutes of Health Research and Health Canada. One study coauthor reported receiving personal fees from Purdue Pharma and the Nova Scotia College of Physicians and Surgeons.

SOURCE: Busse JW et al. JAMA. 2018;320(23):2448-60.

Compared with placebo, opioids provide very modest improvements in chronic noncancer pain and physical functioning that decrease over time, according to the authors of a systematic review and meta-analysis of nearly 100 randomized clinical trials.

There was little difference in pain control between opioids and nonopioid alternatives such as NSAIDs in a subset of nine such comparative trials, reported the authors, led by Jason W. Busse, DC, PhD, of the department of anesthesia at McMaster University, Hamilton, Ont.

Pain benefits of opioids decreased over time in longer trials, possibly because of opioid tolerance or hyperalgesia, a condition marked by hypersensitivity to pain. “A reduced association with benefit over time might lead to prescription of higher opioid doses and consequent harms,” Dr. Busse and his coauthors wrote in JAMA.

The meta-analysis included 96 randomized clinical trials including 26,169 patients with chronic noncancer pain.

Opioid treatment did significantly improve pain and physical function versus placebo, though the magnitude of benefit was small, according to the investigators. The reduction in pain was –0.69 cm on a 10-cm visual analog scale (P less than .001), based on high-quality evidence from 42 randomized, controlled trials that followed patients for at least 3 months.

The improvement in physical functioning was likewise significant but small at 2.04 out of 100 points on the SF-36 physical component score (P less than .001). Emotional and role functioning were not significantly improved by opioid use.

Opioid use was linked to increased vomiting incidence versus placebo, with a relative risk of 4.12 (95% CI, 3.34-5.07; P less than .001) for patients in “nonenrichment” trials – those studies that included all patients regardless of whether or not they reported lack of improvement or had substantial adverse events during a study run-in period.

Nausea, constipation, dizziness, drowsiness, pruritus, and dry mouth were also linked to opioid use as compared with placebo, Dr. Busse and his colleagues reported.

The benefit of opioids and nonopioid alternatives appeared to be similar in this meta-analysis, though the available evidence from comparative studies was of low to moderate quality, the authors advised.

In moderate-quality evidence from nine clinical trials of opioids versus NSAIDs including 1,431 patients, there was no difference in pain relief between the two interventions, the investigators said. Moreover, comparisons of physician functioning also suggested no difference, while opioids were associated with more vomiting.

Both tricyclic antidepressants and synthetic cannabinoids offered similar pain relief, compared with opioids, based on low-quality clinical trial evidence, they added, while moderate-quality evidence suggested opioids offered superior pain relief, compared with anticonvulsants.

Support for the study came from the Canadian Institutes of Health Research and Health Canada. One study coauthor reported receiving personal fees from Purdue Pharma and the Nova Scotia College of Physicians and Surgeons.

SOURCE: Busse JW et al. JAMA. 2018;320(23):2448-60.

Compared with placebo, opioids provide very modest improvements in chronic noncancer pain and physical functioning that decrease over time, according to the authors of a systematic review and meta-analysis of nearly 100 randomized clinical trials.

There was little difference in pain control between opioids and nonopioid alternatives such as NSAIDs in a subset of nine such comparative trials, reported the authors, led by Jason W. Busse, DC, PhD, of the department of anesthesia at McMaster University, Hamilton, Ont.

Pain benefits of opioids decreased over time in longer trials, possibly because of opioid tolerance or hyperalgesia, a condition marked by hypersensitivity to pain. “A reduced association with benefit over time might lead to prescription of higher opioid doses and consequent harms,” Dr. Busse and his coauthors wrote in JAMA.

The meta-analysis included 96 randomized clinical trials including 26,169 patients with chronic noncancer pain.

Opioid treatment did significantly improve pain and physical function versus placebo, though the magnitude of benefit was small, according to the investigators. The reduction in pain was –0.69 cm on a 10-cm visual analog scale (P less than .001), based on high-quality evidence from 42 randomized, controlled trials that followed patients for at least 3 months.

The improvement in physical functioning was likewise significant but small at 2.04 out of 100 points on the SF-36 physical component score (P less than .001). Emotional and role functioning were not significantly improved by opioid use.

Opioid use was linked to increased vomiting incidence versus placebo, with a relative risk of 4.12 (95% CI, 3.34-5.07; P less than .001) for patients in “nonenrichment” trials – those studies that included all patients regardless of whether or not they reported lack of improvement or had substantial adverse events during a study run-in period.

Nausea, constipation, dizziness, drowsiness, pruritus, and dry mouth were also linked to opioid use as compared with placebo, Dr. Busse and his colleagues reported.

The benefit of opioids and nonopioid alternatives appeared to be similar in this meta-analysis, though the available evidence from comparative studies was of low to moderate quality, the authors advised.

In moderate-quality evidence from nine clinical trials of opioids versus NSAIDs including 1,431 patients, there was no difference in pain relief between the two interventions, the investigators said. Moreover, comparisons of physician functioning also suggested no difference, while opioids were associated with more vomiting.

Both tricyclic antidepressants and synthetic cannabinoids offered similar pain relief, compared with opioids, based on low-quality clinical trial evidence, they added, while moderate-quality evidence suggested opioids offered superior pain relief, compared with anticonvulsants.

Support for the study came from the Canadian Institutes of Health Research and Health Canada. One study coauthor reported receiving personal fees from Purdue Pharma and the Nova Scotia College of Physicians and Surgeons.

SOURCE: Busse JW et al. JAMA. 2018;320(23):2448-60.

Although body mass index is criticized for not distinguishing fat from lean mass, its ability to detect subclinical cardiometabolic abnormalities was on par with more sophisticated body scanning technology, according a recent analysis.

BMI and dual-energy x-ray absorptiometry (DXA) had similar associations with cardiometabolic traits associated with coronary heart disease in individuals evaluated at 10 and 18 years of age in a population-based birth cohort study, the study investigators said.

Changes over time in BMI and DXA also were strongly associated with changes in blood pressure, cholesterol, and other markers, according to Joshua A. Bell, PhD, of MRC Integrative Epidemiology Unit, University of Bristol, England, and his coinvestigators.

“Altogether, the results support abdominal fatness as a primary driver of cardiometabolic dysfunction and BMI as a useful tool for detecting its effects,” Dr. Bell and his colleagues said in a report on the study appearing in the Journal of the American College of Cardiology.

In their analysis, Dr. Bell and coinvestigators used Pearson correlation coefficients to compare BMI and total and regional fat indexes from DXA in offspring participants from ALSPAC, (the Avon Longitudinal Study of Parents and Children), in which BMI and DXA measurements were collected at 10 and 18 years of age.

Researchers identified a total of 2,840 participants with at least one measurement at each of those time points. The mean BMI was 17.5 kg/m² at 10 years of age and 22.7 kg/m² at 18 years of age, with greater than 10% of participants classified as obese at each of those time points.


High BMI and high total fat mass index were similarly associated with a variety of cardiometabolic traits, including systolic and diastolic blood pressure, higher low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) cholesterol levels and lower high-density lipoprotein (HDL) cholesterol levels, and more inflammation, investigators found.

BMI was strongly correlated with DXA total and regional fat indexes at 10 years of age, and again at 18 years of age, they reported.

Moreover, gains in BMI from 10 to 18 years of age were strongly associated with higher blood pressure, higher LDL and VLDL cholesterol, lower HDL cholesterol, and other cardiometabolic traits, while associations between DXA measurements and those traits closely tracked those of BMI in pattern and magnitude, investigators added.

Fatness is most often measured in populations using BMI, and causal analyses suggest linkage between higher BMI and coronary heart disease and its intermediates, including blood pressure, LDL and remnant cholesterol, and glucose; despite that, BMI is often disparaged as a tool for assessing cardiometabolic abnormalities because it does not distinguish fat from lean mass and cannot quantify fat distribution, investigators said.

However, based on results of this analysis, it is reasonable to depend on BMI to indirectly measure body and abdominal fatness in future studies, they said in their report.

Dr. Bell and his colleagues reported that they had no relationships relevant to the study publication.

SOURCE: Bell JA et al. J Am Coll Cardiol. 2018 Dec 18;72(24):3142-54.

Although body mass index is criticized for not distinguishing fat from lean mass, its ability to detect subclinical cardiometabolic abnormalities was on par with more sophisticated body scanning technology, according a recent analysis.

BMI and dual-energy x-ray absorptiometry (DXA) had similar associations with cardiometabolic traits associated with coronary heart disease in individuals evaluated at 10 and 18 years of age in a population-based birth cohort study, the study investigators said.

Changes over time in BMI and DXA also were strongly associated with changes in blood pressure, cholesterol, and other markers, according to Joshua A. Bell, PhD, of MRC Integrative Epidemiology Unit, University of Bristol, England, and his coinvestigators.

“Altogether, the results support abdominal fatness as a primary driver of cardiometabolic dysfunction and BMI as a useful tool for detecting its effects,” Dr. Bell and his colleagues said in a report on the study appearing in the Journal of the American College of Cardiology.

In their analysis, Dr. Bell and coinvestigators used Pearson correlation coefficients to compare BMI and total and regional fat indexes from DXA in offspring participants from ALSPAC, (the Avon Longitudinal Study of Parents and Children), in which BMI and DXA measurements were collected at 10 and 18 years of age.

Researchers identified a total of 2,840 participants with at least one measurement at each of those time points. The mean BMI was 17.5 kg/m² at 10 years of age and 22.7 kg/m² at 18 years of age, with greater than 10% of participants classified as obese at each of those time points.


High BMI and high total fat mass index were similarly associated with a variety of cardiometabolic traits, including systolic and diastolic blood pressure, higher low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) cholesterol levels and lower high-density lipoprotein (HDL) cholesterol levels, and more inflammation, investigators found.

BMI was strongly correlated with DXA total and regional fat indexes at 10 years of age, and again at 18 years of age, they reported.

Moreover, gains in BMI from 10 to 18 years of age were strongly associated with higher blood pressure, higher LDL and VLDL cholesterol, lower HDL cholesterol, and other cardiometabolic traits, while associations between DXA measurements and those traits closely tracked those of BMI in pattern and magnitude, investigators added.

Fatness is most often measured in populations using BMI, and causal analyses suggest linkage between higher BMI and coronary heart disease and its intermediates, including blood pressure, LDL and remnant cholesterol, and glucose; despite that, BMI is often disparaged as a tool for assessing cardiometabolic abnormalities because it does not distinguish fat from lean mass and cannot quantify fat distribution, investigators said.

However, based on results of this analysis, it is reasonable to depend on BMI to indirectly measure body and abdominal fatness in future studies, they said in their report.

Dr. Bell and his colleagues reported that they had no relationships relevant to the study publication.

SOURCE: Bell JA et al. J Am Coll Cardiol. 2018 Dec 18;72(24):3142-54.

Although body mass index is criticized for not distinguishing fat from lean mass, its ability to detect subclinical cardiometabolic abnormalities was on par with more sophisticated body scanning technology, according a recent analysis.

BMI and dual-energy x-ray absorptiometry (DXA) had similar associations with cardiometabolic traits associated with coronary heart disease in individuals evaluated at 10 and 18 years of age in a population-based birth cohort study, the study investigators said.

Changes over time in BMI and DXA also were strongly associated with changes in blood pressure, cholesterol, and other markers, according to Joshua A. Bell, PhD, of MRC Integrative Epidemiology Unit, University of Bristol, England, and his coinvestigators.

“Altogether, the results support abdominal fatness as a primary driver of cardiometabolic dysfunction and BMI as a useful tool for detecting its effects,” Dr. Bell and his colleagues said in a report on the study appearing in the Journal of the American College of Cardiology.

In their analysis, Dr. Bell and coinvestigators used Pearson correlation coefficients to compare BMI and total and regional fat indexes from DXA in offspring participants from ALSPAC, (the Avon Longitudinal Study of Parents and Children), in which BMI and DXA measurements were collected at 10 and 18 years of age.

Researchers identified a total of 2,840 participants with at least one measurement at each of those time points. The mean BMI was 17.5 kg/m² at 10 years of age and 22.7 kg/m² at 18 years of age, with greater than 10% of participants classified as obese at each of those time points.


High BMI and high total fat mass index were similarly associated with a variety of cardiometabolic traits, including systolic and diastolic blood pressure, higher low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) cholesterol levels and lower high-density lipoprotein (HDL) cholesterol levels, and more inflammation, investigators found.

BMI was strongly correlated with DXA total and regional fat indexes at 10 years of age, and again at 18 years of age, they reported.

Moreover, gains in BMI from 10 to 18 years of age were strongly associated with higher blood pressure, higher LDL and VLDL cholesterol, lower HDL cholesterol, and other cardiometabolic traits, while associations between DXA measurements and those traits closely tracked those of BMI in pattern and magnitude, investigators added.

Fatness is most often measured in populations using BMI, and causal analyses suggest linkage between higher BMI and coronary heart disease and its intermediates, including blood pressure, LDL and remnant cholesterol, and glucose; despite that, BMI is often disparaged as a tool for assessing cardiometabolic abnormalities because it does not distinguish fat from lean mass and cannot quantify fat distribution, investigators said.

However, based on results of this analysis, it is reasonable to depend on BMI to indirectly measure body and abdominal fatness in future studies, they said in their report.

Dr. Bell and his colleagues reported that they had no relationships relevant to the study publication.

SOURCE: Bell JA et al. J Am Coll Cardiol. 2018 Dec 18;72(24):3142-54.

Photo by Rod Waddington

SAN DIEGO—An inexpensive, rapid, and easy-to-use blood test accurately detected sickle cell disease in young children in Uganda, according to a speaker at the 2018 ASH Annual Meeting.

The test, called HemoTypeSC, uses monoclonal antibodies to detect hemoglobins A, S, and C in a drop of whole blood.

HemoTypeSC costs less than $2 to the end user and delivers results in about 10 minutes.

“This is ideal for use in resource-constrained regions of high prevalence, such as Africa and central India,” said Erik Serrao, PhD, of Silver Lake Research in Azusa, California.

“Early screening plus treatment plus counseling equals saving millions of lives over the coming decades, and we believe HemoTypeSC can form an integral part of the initial part of this equation.”

Dr. Serrao reported results from a study of HemoTypeSC during the late-breaking abstracts session at ASH (abstract LBA-3).

He and his colleagues compared results with the HemoTypeSC test to results with hemoglobin electrophoresis for detection of the phenotypes HbAA (normal), HbAS (sickle cell trait), and HbSS (sickle cell disease).

The investigators compared these two testing methods in 1,000 children between the ages of 1 month and 5 years who were prospectively recruited from hospital wards and outpatient clinics in Uganda.

Results

The initial analysis suggested HemoTypeSC had an overall accuracy of 99.8%, correctly identifying 998 of 1,000 phenotypes as initially determined by electrophoresis.

HemoTypeSC correctly identified 100% of the 720 HbAA specimens and 100% of 182 HbAS specimens.

HemoTypeSC identified as HbSS 98% (96/98) of specimens that were identified as HbSS by electrophoresis. This left two discordant samples, both of which HemoTypeSC identified as HbAS.

Investigators subsequently discovered that both individuals with the discordant samples had previously been diagnosed with sickle cell disease and had received recent transfusions with HbAA blood.

“Therefore, the true phenotype at the time of testing for these samples was HbAS, as hemoglobin A and S were both in the blood,” Dr. Serrao said.

This brought the accuracy rate of HemoTypeSC up to 100%.

Dr. Serrao noted that this study excluded newborns. However, a different study of HemoTypeSC, recently published in the American Journal of Hematology, demonstrated 100% accuracy across multiple phenotypes in the setting of newborn screening.

Implications

Of all the late-breaking abstracts at ASH this year, the study by Dr. Serrao and his colleagues is the one with the potential to save the most lives, according to Mark Crowther, MD, of McMaster University in Hamilton, Ontario, Canada.

He said using current gold-standard methods for diagnosing sickle cell disease is, at minimum, challenging and “frankly impossible” in many low-resource settings because of the cost and the requirement for sophisticated equipment and reliable electricity.

However, he believes HemoTypeSC could change that.

“The ability to diagnose sickle cell disease early and intervene early will result in potentially thousands of infants, who would otherwise die in infancy or early childhood, surviving into adulthood,” Dr. Crowther said.

Dr. Serrao noted that sickle cell disease screening programs have been projected to be cost-effective in Africa. Such programs could even save money for governments over time as budgets are reallocated toward screening, with less money needed for treatment of patients presenting with severe complications in hospitals.

Dr. Serrao reported that he is an employee of Silver Lake Research, which funded this study, approved the study design, and donated HemoTypeSC tests.

Photo by Rod Waddington

SAN DIEGO—An inexpensive, rapid, and easy-to-use blood test accurately detected sickle cell disease in young children in Uganda, according to a speaker at the 2018 ASH Annual Meeting.

The test, called HemoTypeSC, uses monoclonal antibodies to detect hemoglobins A, S, and C in a drop of whole blood.

HemoTypeSC costs less than $2 to the end user and delivers results in about 10 minutes.

“This is ideal for use in resource-constrained regions of high prevalence, such as Africa and central India,” said Erik Serrao, PhD, of Silver Lake Research in Azusa, California.

“Early screening plus treatment plus counseling equals saving millions of lives over the coming decades, and we believe HemoTypeSC can form an integral part of the initial part of this equation.”

Dr. Serrao reported results from a study of HemoTypeSC during the late-breaking abstracts session at ASH (abstract LBA-3).

He and his colleagues compared results with the HemoTypeSC test to results with hemoglobin electrophoresis for detection of the phenotypes HbAA (normal), HbAS (sickle cell trait), and HbSS (sickle cell disease).

The investigators compared these two testing methods in 1,000 children between the ages of 1 month and 5 years who were prospectively recruited from hospital wards and outpatient clinics in Uganda.

Results

The initial analysis suggested HemoTypeSC had an overall accuracy of 99.8%, correctly identifying 998 of 1,000 phenotypes as initially determined by electrophoresis.

HemoTypeSC correctly identified 100% of the 720 HbAA specimens and 100% of 182 HbAS specimens.

HemoTypeSC identified as HbSS 98% (96/98) of specimens that were identified as HbSS by electrophoresis. This left two discordant samples, both of which HemoTypeSC identified as HbAS.

Investigators subsequently discovered that both individuals with the discordant samples had previously been diagnosed with sickle cell disease and had received recent transfusions with HbAA blood.

“Therefore, the true phenotype at the time of testing for these samples was HbAS, as hemoglobin A and S were both in the blood,” Dr. Serrao said.

This brought the accuracy rate of HemoTypeSC up to 100%.

Dr. Serrao noted that this study excluded newborns. However, a different study of HemoTypeSC, recently published in the American Journal of Hematology, demonstrated 100% accuracy across multiple phenotypes in the setting of newborn screening.

Implications

Of all the late-breaking abstracts at ASH this year, the study by Dr. Serrao and his colleagues is the one with the potential to save the most lives, according to Mark Crowther, MD, of McMaster University in Hamilton, Ontario, Canada.

He said using current gold-standard methods for diagnosing sickle cell disease is, at minimum, challenging and “frankly impossible” in many low-resource settings because of the cost and the requirement for sophisticated equipment and reliable electricity.

However, he believes HemoTypeSC could change that.

“The ability to diagnose sickle cell disease early and intervene early will result in potentially thousands of infants, who would otherwise die in infancy or early childhood, surviving into adulthood,” Dr. Crowther said.

Dr. Serrao noted that sickle cell disease screening programs have been projected to be cost-effective in Africa. Such programs could even save money for governments over time as budgets are reallocated toward screening, with less money needed for treatment of patients presenting with severe complications in hospitals.

Dr. Serrao reported that he is an employee of Silver Lake Research, which funded this study, approved the study design, and donated HemoTypeSC tests.

Photo by Rod Waddington

SAN DIEGO—An inexpensive, rapid, and easy-to-use blood test accurately detected sickle cell disease in young children in Uganda, according to a speaker at the 2018 ASH Annual Meeting.

The test, called HemoTypeSC, uses monoclonal antibodies to detect hemoglobins A, S, and C in a drop of whole blood.

HemoTypeSC costs less than $2 to the end user and delivers results in about 10 minutes.

“This is ideal for use in resource-constrained regions of high prevalence, such as Africa and central India,” said Erik Serrao, PhD, of Silver Lake Research in Azusa, California.

“Early screening plus treatment plus counseling equals saving millions of lives over the coming decades, and we believe HemoTypeSC can form an integral part of the initial part of this equation.”

Dr. Serrao reported results from a study of HemoTypeSC during the late-breaking abstracts session at ASH (abstract LBA-3).

He and his colleagues compared results with the HemoTypeSC test to results with hemoglobin electrophoresis for detection of the phenotypes HbAA (normal), HbAS (sickle cell trait), and HbSS (sickle cell disease).

The investigators compared these two testing methods in 1,000 children between the ages of 1 month and 5 years who were prospectively recruited from hospital wards and outpatient clinics in Uganda.

Results

The initial analysis suggested HemoTypeSC had an overall accuracy of 99.8%, correctly identifying 998 of 1,000 phenotypes as initially determined by electrophoresis.

HemoTypeSC correctly identified 100% of the 720 HbAA specimens and 100% of 182 HbAS specimens.

HemoTypeSC identified as HbSS 98% (96/98) of specimens that were identified as HbSS by electrophoresis. This left two discordant samples, both of which HemoTypeSC identified as HbAS.

Investigators subsequently discovered that both individuals with the discordant samples had previously been diagnosed with sickle cell disease and had received recent transfusions with HbAA blood.

“Therefore, the true phenotype at the time of testing for these samples was HbAS, as hemoglobin A and S were both in the blood,” Dr. Serrao said.

This brought the accuracy rate of HemoTypeSC up to 100%.

Dr. Serrao noted that this study excluded newborns. However, a different study of HemoTypeSC, recently published in the American Journal of Hematology, demonstrated 100% accuracy across multiple phenotypes in the setting of newborn screening.

Implications

Of all the late-breaking abstracts at ASH this year, the study by Dr. Serrao and his colleagues is the one with the potential to save the most lives, according to Mark Crowther, MD, of McMaster University in Hamilton, Ontario, Canada.

He said using current gold-standard methods for diagnosing sickle cell disease is, at minimum, challenging and “frankly impossible” in many low-resource settings because of the cost and the requirement for sophisticated equipment and reliable electricity.

However, he believes HemoTypeSC could change that.

“The ability to diagnose sickle cell disease early and intervene early will result in potentially thousands of infants, who would otherwise die in infancy or early childhood, surviving into adulthood,” Dr. Crowther said.

Dr. Serrao noted that sickle cell disease screening programs have been projected to be cost-effective in Africa. Such programs could even save money for governments over time as budgets are reallocated toward screening, with less money needed for treatment of patients presenting with severe complications in hospitals.

Dr. Serrao reported that he is an employee of Silver Lake Research, which funded this study, approved the study design, and donated HemoTypeSC tests.

In patients with renal cell carcinoma, trough concentrations of pazopanib in a specific target range were associated with better safety and comparable efficacy, versus higher concentrations of the drug, authors of an exploratory investigation have reported.

Fewer serious toxicities were seen in patients with pazopanib concentrations in the 20- to 50-mcg/mL range, yet overall response rate was similar compared to patients with concentrations over 50 mcg/mL, according to results of the retrospective study.

The findings suggest therapeutic drug monitoring to achieve a specific trough concentration may be useful to optimize pazopanib dosing, according to investigator Tomohiro Terada, PhD, of Shiga University of Medical Science Hospital, Japan, and coinvestigators.

Therapeutic drug monitoring for sunitinib in RCC patients was recently covered by medical insurance in Japan, Dr. Terada and colleagues wrote in Clinical Genitourinary Cancer.

The strategy may be especially suited to adjusting the dose of pazopanib, which is often associated with severe toxicities and has pharmacokinetics that suggest a wide variation between individuals, they added.

The retrospective study by Dr. Terada and colleagues included 27 renal cell carcinoma patients who received pazopanib at doses of 400, 600, or 800 mg daily based on the recommendation of the treating physician, with doses reduced or discontinued based on adverse events or progression.

Trough concentrations of pazopanib 3 months after starting the treatment ranged from a low of 10.6 mcg/mL to a high of 106 mcg/mL, with a median of 49.1 mcg/mL, according to the report.

One-third of patients experienced grade 3 or greater toxicities, including anorexia, hypertension, anemia, and thrombocytopenia, among others. The median pazopanib concentration for those nine patients was 69.3 mcg/mL, compared with 41.2 mcg/mL for those not experiencing serious toxicities (P less than .05).

A concentration over 50.3 mcg/mL predicted grade 3 or greater toxicity, statistical analysis showed, with 8 out of 13 patients with concentrations above that threshold experiencing serious toxicities. By contrast, 1 of 14 patients below that threshold experienced grade 3 or greater toxicities.

No responses were observed in three patients with pazopanib concentrations below 20.5 mcg/mL, a concentration level considered to be subtherapeutic based on previous investigations.

Overall response rates were similar for patients with concentrations in the “optimal” 20.5- and 50.3-mcg/mL range and those with concentrations over 50.3 mcg/mL, according to the investigators.

Among 11 patients in that “optimal” range, partial responses were seen in 5, they reported, while for the 13 patients with high concentrations of the drug, partial responses were seen in 4 patients and a complete response was seen in 1 patient.

Trough concentrations may not predict all types of toxicities, according to the investigators, who said that the results of their small, retrospective analysis should be validated in a large, prospective study.

In particular, there was no significant relationship between trough concentration of pazopanib and development of grade 2 or greater hepatotoxicity, a common and specific side effect of the drug.

“Based on these findings, pazopanib-induced hepatotoxicity may not be related to the pharmacokinetics of pazopanib,” they wrote. “Therefore, pharmacogenomics testing is needed to predict pazopanib-induced hepatotoxicity.”

Dr. Terada and coauthors said they had no conflicts of interest to report.
 

SOURCE: Noda S et al. Clin Genitourin Cancer. 2018 Dec 7. doi: 10.1016/j.clgc.2018.12.001.

In patients with renal cell carcinoma, trough concentrations of pazopanib in a specific target range were associated with better safety and comparable efficacy, versus higher concentrations of the drug, authors of an exploratory investigation have reported.

Fewer serious toxicities were seen in patients with pazopanib concentrations in the 20- to 50-mcg/mL range, yet overall response rate was similar compared to patients with concentrations over 50 mcg/mL, according to results of the retrospective study.

The findings suggest therapeutic drug monitoring to achieve a specific trough concentration may be useful to optimize pazopanib dosing, according to investigator Tomohiro Terada, PhD, of Shiga University of Medical Science Hospital, Japan, and coinvestigators.

Therapeutic drug monitoring for sunitinib in RCC patients was recently covered by medical insurance in Japan, Dr. Terada and colleagues wrote in Clinical Genitourinary Cancer.

The strategy may be especially suited to adjusting the dose of pazopanib, which is often associated with severe toxicities and has pharmacokinetics that suggest a wide variation between individuals, they added.

The retrospective study by Dr. Terada and colleagues included 27 renal cell carcinoma patients who received pazopanib at doses of 400, 600, or 800 mg daily based on the recommendation of the treating physician, with doses reduced or discontinued based on adverse events or progression.

Trough concentrations of pazopanib 3 months after starting the treatment ranged from a low of 10.6 mcg/mL to a high of 106 mcg/mL, with a median of 49.1 mcg/mL, according to the report.

One-third of patients experienced grade 3 or greater toxicities, including anorexia, hypertension, anemia, and thrombocytopenia, among others. The median pazopanib concentration for those nine patients was 69.3 mcg/mL, compared with 41.2 mcg/mL for those not experiencing serious toxicities (P less than .05).

A concentration over 50.3 mcg/mL predicted grade 3 or greater toxicity, statistical analysis showed, with 8 out of 13 patients with concentrations above that threshold experiencing serious toxicities. By contrast, 1 of 14 patients below that threshold experienced grade 3 or greater toxicities.

No responses were observed in three patients with pazopanib concentrations below 20.5 mcg/mL, a concentration level considered to be subtherapeutic based on previous investigations.

Overall response rates were similar for patients with concentrations in the “optimal” 20.5- and 50.3-mcg/mL range and those with concentrations over 50.3 mcg/mL, according to the investigators.

Among 11 patients in that “optimal” range, partial responses were seen in 5, they reported, while for the 13 patients with high concentrations of the drug, partial responses were seen in 4 patients and a complete response was seen in 1 patient.

Trough concentrations may not predict all types of toxicities, according to the investigators, who said that the results of their small, retrospective analysis should be validated in a large, prospective study.

In particular, there was no significant relationship between trough concentration of pazopanib and development of grade 2 or greater hepatotoxicity, a common and specific side effect of the drug.

“Based on these findings, pazopanib-induced hepatotoxicity may not be related to the pharmacokinetics of pazopanib,” they wrote. “Therefore, pharmacogenomics testing is needed to predict pazopanib-induced hepatotoxicity.”

Dr. Terada and coauthors said they had no conflicts of interest to report.
 

SOURCE: Noda S et al. Clin Genitourin Cancer. 2018 Dec 7. doi: 10.1016/j.clgc.2018.12.001.

In patients with renal cell carcinoma, trough concentrations of pazopanib in a specific target range were associated with better safety and comparable efficacy, versus higher concentrations of the drug, authors of an exploratory investigation have reported.

Fewer serious toxicities were seen in patients with pazopanib concentrations in the 20- to 50-mcg/mL range, yet overall response rate was similar compared to patients with concentrations over 50 mcg/mL, according to results of the retrospective study.

The findings suggest therapeutic drug monitoring to achieve a specific trough concentration may be useful to optimize pazopanib dosing, according to investigator Tomohiro Terada, PhD, of Shiga University of Medical Science Hospital, Japan, and coinvestigators.

Therapeutic drug monitoring for sunitinib in RCC patients was recently covered by medical insurance in Japan, Dr. Terada and colleagues wrote in Clinical Genitourinary Cancer.

The strategy may be especially suited to adjusting the dose of pazopanib, which is often associated with severe toxicities and has pharmacokinetics that suggest a wide variation between individuals, they added.

The retrospective study by Dr. Terada and colleagues included 27 renal cell carcinoma patients who received pazopanib at doses of 400, 600, or 800 mg daily based on the recommendation of the treating physician, with doses reduced or discontinued based on adverse events or progression.

Trough concentrations of pazopanib 3 months after starting the treatment ranged from a low of 10.6 mcg/mL to a high of 106 mcg/mL, with a median of 49.1 mcg/mL, according to the report.

One-third of patients experienced grade 3 or greater toxicities, including anorexia, hypertension, anemia, and thrombocytopenia, among others. The median pazopanib concentration for those nine patients was 69.3 mcg/mL, compared with 41.2 mcg/mL for those not experiencing serious toxicities (P less than .05).

A concentration over 50.3 mcg/mL predicted grade 3 or greater toxicity, statistical analysis showed, with 8 out of 13 patients with concentrations above that threshold experiencing serious toxicities. By contrast, 1 of 14 patients below that threshold experienced grade 3 or greater toxicities.

No responses were observed in three patients with pazopanib concentrations below 20.5 mcg/mL, a concentration level considered to be subtherapeutic based on previous investigations.

Overall response rates were similar for patients with concentrations in the “optimal” 20.5- and 50.3-mcg/mL range and those with concentrations over 50.3 mcg/mL, according to the investigators.

Among 11 patients in that “optimal” range, partial responses were seen in 5, they reported, while for the 13 patients with high concentrations of the drug, partial responses were seen in 4 patients and a complete response was seen in 1 patient.

Trough concentrations may not predict all types of toxicities, according to the investigators, who said that the results of their small, retrospective analysis should be validated in a large, prospective study.

In particular, there was no significant relationship between trough concentration of pazopanib and development of grade 2 or greater hepatotoxicity, a common and specific side effect of the drug.

“Based on these findings, pazopanib-induced hepatotoxicity may not be related to the pharmacokinetics of pazopanib,” they wrote. “Therefore, pharmacogenomics testing is needed to predict pazopanib-induced hepatotoxicity.”

Dr. Terada and coauthors said they had no conflicts of interest to report.
 

SOURCE: Noda S et al. Clin Genitourin Cancer. 2018 Dec 7. doi: 10.1016/j.clgc.2018.12.001.

Rivaroxaban

SAN DIEGO—In the phase 3 CASSINI trial, prophylaxis with rivaroxaban reduced the rate of venous thromboembolism (VTE) and VTE-related death in high-risk ambulatory cancer patients receiving systemic therapy.

The reduction in VTE and related death was not statistically significant in the primary analysis, which included a period of time after treatment had stopped.

However, the reduction in VTE and related death was significant in a prespecified secondary analysis limited to the on-treatment period.

Alok A. Khorana, MD, of the Cleveland Clinic in Ohio, presented these results at the 2018 ASH Annual Meeting (abstract LBA-1).

The trial (NCT02555878) included 841 patients enrolled at 143 centers in 11 countries. The patients had solid tumor malignancies or lymphomas and a high risk of VTE (Khorana score of 2 or greater).

The patients were randomized to either rivaroxaban at 10 mg once daily (n=420) or placebo once daily (n=421).

In the primary analysis period of 180 days, the composite endpoint of VTE or VTE-related death occurred in 5.95% of the rivaroxaban-treated group and 8.79% of the placebo group (hazard ratio [HR]=0.66; 95% confidence interval [CI], 0.40-1.09; P=0.101).

However, 177 patients (43.7%) in the rivaroxaban group stopped treatment before the 180-day mark, as did 203 patients (50.2%) in the placebo group.

In a prespecified secondary analysis looking only at the treatment period, rivaroxaban did significantly reduce the risk of VTE and VTE-related death, Dr. Khorana said. The composite endpoint occurred in 2.62% of rivaroxaban-treated patients and 6.41% of placebo-treated patients in that analysis (HR=0.40; 95% CI, 0.20-0.80; P=0.007).

Rates of major bleeding and clinically relevant nonmajor bleeding were not significantly different between the groups.

Major bleeding occurred in 1.98% (n=8) of rivaroxaban-treated patients and 0.99% (n=4) of placebo-treated patients (HR=1.96, 0.59-6.49; P=0.265).

Clinically relevant nonmajor bleeding occurred in 2.72% (n=11) and 1.98% (n=8), respectively (HR=1.34, 95% CI, 0.54-3.32; P=0.532).

CASSINI was sponsored by Bayer and Janssen. Dr. Khorana reported relationships with Janssen, Pharmacyclics, PharmaCyte, TriSalus Life Sciences, PAREXEL, Pfizer, Sanofi, Halozyme, Seattle Genetics, AngioDynamics, LEO Pharma, Medscape/WebMD, and Bayer.

Rivaroxaban

SAN DIEGO—In the phase 3 CASSINI trial, prophylaxis with rivaroxaban reduced the rate of venous thromboembolism (VTE) and VTE-related death in high-risk ambulatory cancer patients receiving systemic therapy.

The reduction in VTE and related death was not statistically significant in the primary analysis, which included a period of time after treatment had stopped.

However, the reduction in VTE and related death was significant in a prespecified secondary analysis limited to the on-treatment period.

Alok A. Khorana, MD, of the Cleveland Clinic in Ohio, presented these results at the 2018 ASH Annual Meeting (abstract LBA-1).

The trial (NCT02555878) included 841 patients enrolled at 143 centers in 11 countries. The patients had solid tumor malignancies or lymphomas and a high risk of VTE (Khorana score of 2 or greater).

The patients were randomized to either rivaroxaban at 10 mg once daily (n=420) or placebo once daily (n=421).

In the primary analysis period of 180 days, the composite endpoint of VTE or VTE-related death occurred in 5.95% of the rivaroxaban-treated group and 8.79% of the placebo group (hazard ratio [HR]=0.66; 95% confidence interval [CI], 0.40-1.09; P=0.101).

However, 177 patients (43.7%) in the rivaroxaban group stopped treatment before the 180-day mark, as did 203 patients (50.2%) in the placebo group.

In a prespecified secondary analysis looking only at the treatment period, rivaroxaban did significantly reduce the risk of VTE and VTE-related death, Dr. Khorana said. The composite endpoint occurred in 2.62% of rivaroxaban-treated patients and 6.41% of placebo-treated patients in that analysis (HR=0.40; 95% CI, 0.20-0.80; P=0.007).

Rates of major bleeding and clinically relevant nonmajor bleeding were not significantly different between the groups.

Major bleeding occurred in 1.98% (n=8) of rivaroxaban-treated patients and 0.99% (n=4) of placebo-treated patients (HR=1.96, 0.59-6.49; P=0.265).

Clinically relevant nonmajor bleeding occurred in 2.72% (n=11) and 1.98% (n=8), respectively (HR=1.34, 95% CI, 0.54-3.32; P=0.532).

CASSINI was sponsored by Bayer and Janssen. Dr. Khorana reported relationships with Janssen, Pharmacyclics, PharmaCyte, TriSalus Life Sciences, PAREXEL, Pfizer, Sanofi, Halozyme, Seattle Genetics, AngioDynamics, LEO Pharma, Medscape/WebMD, and Bayer.

Rivaroxaban

SAN DIEGO—In the phase 3 CASSINI trial, prophylaxis with rivaroxaban reduced the rate of venous thromboembolism (VTE) and VTE-related death in high-risk ambulatory cancer patients receiving systemic therapy.

The reduction in VTE and related death was not statistically significant in the primary analysis, which included a period of time after treatment had stopped.

However, the reduction in VTE and related death was significant in a prespecified secondary analysis limited to the on-treatment period.

Alok A. Khorana, MD, of the Cleveland Clinic in Ohio, presented these results at the 2018 ASH Annual Meeting (abstract LBA-1).

The trial (NCT02555878) included 841 patients enrolled at 143 centers in 11 countries. The patients had solid tumor malignancies or lymphomas and a high risk of VTE (Khorana score of 2 or greater).

The patients were randomized to either rivaroxaban at 10 mg once daily (n=420) or placebo once daily (n=421).

In the primary analysis period of 180 days, the composite endpoint of VTE or VTE-related death occurred in 5.95% of the rivaroxaban-treated group and 8.79% of the placebo group (hazard ratio [HR]=0.66; 95% confidence interval [CI], 0.40-1.09; P=0.101).

However, 177 patients (43.7%) in the rivaroxaban group stopped treatment before the 180-day mark, as did 203 patients (50.2%) in the placebo group.

In a prespecified secondary analysis looking only at the treatment period, rivaroxaban did significantly reduce the risk of VTE and VTE-related death, Dr. Khorana said. The composite endpoint occurred in 2.62% of rivaroxaban-treated patients and 6.41% of placebo-treated patients in that analysis (HR=0.40; 95% CI, 0.20-0.80; P=0.007).

Rates of major bleeding and clinically relevant nonmajor bleeding were not significantly different between the groups.

Major bleeding occurred in 1.98% (n=8) of rivaroxaban-treated patients and 0.99% (n=4) of placebo-treated patients (HR=1.96, 0.59-6.49; P=0.265).

Clinically relevant nonmajor bleeding occurred in 2.72% (n=11) and 1.98% (n=8), respectively (HR=1.34, 95% CI, 0.54-3.32; P=0.532).

CASSINI was sponsored by Bayer and Janssen. Dr. Khorana reported relationships with Janssen, Pharmacyclics, PharmaCyte, TriSalus Life Sciences, PAREXEL, Pfizer, Sanofi, Halozyme, Seattle Genetics, AngioDynamics, LEO Pharma, Medscape/WebMD, and Bayer.

While patients with renal cell carcinoma (RCC) brain metastases are traditionally thought of as having a grim prognosis, a subset of patients may experience durable long-term survival with cytoreductive nephrectomy, authors of a retrospective study have reported.

Specifically, patients with brain lesions and no additional metastatic disease sites who underwent cytoreduction had a 2-year survival rate of 52%, according to the researchers’ analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Program. 

By contrast, these patients with brain-only metastases who did not undergo the procedure had a 2-year survival of 14%, reported Gennady Bratslavsky, MD, of State University of New York, Syracuse, and his associates.

The findings are at odds with “previously accepted dogma” that surgery is inadvisable in patients with RCC with brain metastases, which is traditionally thought of as a poor-risk feature, according to Dr. Bratslavsky and his colleagues.

“These patients seem to benefit from cytoreductive nephrectomy and may potentially be excellent candidates for clinical trials,” they wrote in Urologic Oncology.

However, patient selection likely drove survival outcomes in this retrospective cohort, the authors acknowledged, adding that they did not intend to argue “for or against” the role of cytoreductive nephrectomy.

In their analysis, they identified 6,403 patients with metastatic RCC and complete information on sites of metastasis; of these, 775 (12.1%) had brain metastases.

Patients with brain metastases generally fared worse than did patients with other, non-brain metastases, with 2-year survival rates of 14.9% and 28.6%, respectively (P less than .0001); however, patients with brain-only metastases had a 2-year survival of 31% overall in this analysis.

Cytoreductive nephrectomy was performed in 40.8% of patients with brain-only metastases, versus 20.8% of patients with synchronous metastases (P less than .0001).

Brain-only metastases patients who underwent cytoreductive nephrectomy had 1-year survival of 67%, 2-year survival of 52%, and median survival of 33 months, the data show. In contrast, brain-only metastases patients who did not undergo the procedure had 1-year survival of 26%, 2-year survival of 14%, and median survival of just 5 months.

Even when the researchers included patients with brain metastases in addition to other sites, cytoreduction was associated with superior outcomes, compared with patients with non-brain metastases who did not undergo cytoreduction, the investigators said. The reported 2-year survival rates in that analysis were 34.1% for brain metastasis and cytoreduction versus 14.4% for non-brain metastasis and no cytoreduction.

While this study was retrospective and was based on limited patient data, these findings nevertheless suggest that patients with RCC and isolated brain metastases might benefit from the procedure, Dr. Bratslavsky and his coauthors said.

“We anticipate that this work will be helpful for patient counseling and for modifying future exclusion criteria in clinical trials,” they concluded.

Dr. Bratslavsky and his coauthors listed no disclosures related to their research.

SOURCE: Daugherty M et al. Urol Oncol. 2018 Dec 5. doi: 10.1016/j.urolonc.2018.10.021.

While patients with renal cell carcinoma (RCC) brain metastases are traditionally thought of as having a grim prognosis, a subset of patients may experience durable long-term survival with cytoreductive nephrectomy, authors of a retrospective study have reported.

Specifically, patients with brain lesions and no additional metastatic disease sites who underwent cytoreduction had a 2-year survival rate of 52%, according to the researchers’ analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Program. 

By contrast, these patients with brain-only metastases who did not undergo the procedure had a 2-year survival of 14%, reported Gennady Bratslavsky, MD, of State University of New York, Syracuse, and his associates.

The findings are at odds with “previously accepted dogma” that surgery is inadvisable in patients with RCC with brain metastases, which is traditionally thought of as a poor-risk feature, according to Dr. Bratslavsky and his colleagues.

“These patients seem to benefit from cytoreductive nephrectomy and may potentially be excellent candidates for clinical trials,” they wrote in Urologic Oncology.

However, patient selection likely drove survival outcomes in this retrospective cohort, the authors acknowledged, adding that they did not intend to argue “for or against” the role of cytoreductive nephrectomy.

In their analysis, they identified 6,403 patients with metastatic RCC and complete information on sites of metastasis; of these, 775 (12.1%) had brain metastases.

Patients with brain metastases generally fared worse than did patients with other, non-brain metastases, with 2-year survival rates of 14.9% and 28.6%, respectively (P less than .0001); however, patients with brain-only metastases had a 2-year survival of 31% overall in this analysis.

Cytoreductive nephrectomy was performed in 40.8% of patients with brain-only metastases, versus 20.8% of patients with synchronous metastases (P less than .0001).

Brain-only metastases patients who underwent cytoreductive nephrectomy had 1-year survival of 67%, 2-year survival of 52%, and median survival of 33 months, the data show. In contrast, brain-only metastases patients who did not undergo the procedure had 1-year survival of 26%, 2-year survival of 14%, and median survival of just 5 months.

Even when the researchers included patients with brain metastases in addition to other sites, cytoreduction was associated with superior outcomes, compared with patients with non-brain metastases who did not undergo cytoreduction, the investigators said. The reported 2-year survival rates in that analysis were 34.1% for brain metastasis and cytoreduction versus 14.4% for non-brain metastasis and no cytoreduction.

While this study was retrospective and was based on limited patient data, these findings nevertheless suggest that patients with RCC and isolated brain metastases might benefit from the procedure, Dr. Bratslavsky and his coauthors said.

“We anticipate that this work will be helpful for patient counseling and for modifying future exclusion criteria in clinical trials,” they concluded.

Dr. Bratslavsky and his coauthors listed no disclosures related to their research.

SOURCE: Daugherty M et al. Urol Oncol. 2018 Dec 5. doi: 10.1016/j.urolonc.2018.10.021.

While patients with renal cell carcinoma (RCC) brain metastases are traditionally thought of as having a grim prognosis, a subset of patients may experience durable long-term survival with cytoreductive nephrectomy, authors of a retrospective study have reported.

Specifically, patients with brain lesions and no additional metastatic disease sites who underwent cytoreduction had a 2-year survival rate of 52%, according to the researchers’ analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Program. 

By contrast, these patients with brain-only metastases who did not undergo the procedure had a 2-year survival of 14%, reported Gennady Bratslavsky, MD, of State University of New York, Syracuse, and his associates.

The findings are at odds with “previously accepted dogma” that surgery is inadvisable in patients with RCC with brain metastases, which is traditionally thought of as a poor-risk feature, according to Dr. Bratslavsky and his colleagues.

“These patients seem to benefit from cytoreductive nephrectomy and may potentially be excellent candidates for clinical trials,” they wrote in Urologic Oncology.

However, patient selection likely drove survival outcomes in this retrospective cohort, the authors acknowledged, adding that they did not intend to argue “for or against” the role of cytoreductive nephrectomy.

In their analysis, they identified 6,403 patients with metastatic RCC and complete information on sites of metastasis; of these, 775 (12.1%) had brain metastases.

Patients with brain metastases generally fared worse than did patients with other, non-brain metastases, with 2-year survival rates of 14.9% and 28.6%, respectively (P less than .0001); however, patients with brain-only metastases had a 2-year survival of 31% overall in this analysis.

Cytoreductive nephrectomy was performed in 40.8% of patients with brain-only metastases, versus 20.8% of patients with synchronous metastases (P less than .0001).

Brain-only metastases patients who underwent cytoreductive nephrectomy had 1-year survival of 67%, 2-year survival of 52%, and median survival of 33 months, the data show. In contrast, brain-only metastases patients who did not undergo the procedure had 1-year survival of 26%, 2-year survival of 14%, and median survival of just 5 months.

Even when the researchers included patients with brain metastases in addition to other sites, cytoreduction was associated with superior outcomes, compared with patients with non-brain metastases who did not undergo cytoreduction, the investigators said. The reported 2-year survival rates in that analysis were 34.1% for brain metastasis and cytoreduction versus 14.4% for non-brain metastasis and no cytoreduction.

While this study was retrospective and was based on limited patient data, these findings nevertheless suggest that patients with RCC and isolated brain metastases might benefit from the procedure, Dr. Bratslavsky and his coauthors said.

“We anticipate that this work will be helpful for patient counseling and for modifying future exclusion criteria in clinical trials,” they concluded.

Dr. Bratslavsky and his coauthors listed no disclosures related to their research.

SOURCE: Daugherty M et al. Urol Oncol. 2018 Dec 5. doi: 10.1016/j.urolonc.2018.10.021.

The ratio of apolipoproteins B and A1 (apo B/A1) is an independent prognostic factor in patients with metastatic renal cell carcinoma, according to authors of a recent retrospective study.

The apo B/A1 ratio, evaluated prior to cytoreductive nephrectomy, was significantly linked with poor progression-free survival and overall survival, according to Fan Zhang, MD, of the Chinese PLA General Hospital in Beijing and coauthors.

Those findings suggest that patients with metastatic RCC should receive “consistent follow-up” that includes evaluation of that ratio, Dr. Zhang and colleagues said.

“As a novel prognostic factor, the preoperative apo B/A1 ratio can be utilized as a supplement to improve the current prognostic evaluation and treatment decision for patients with metastatic RCC,” they wrote in Urologic Oncology.

Apo B and A1, which are predominant components of low-density lipoprotein (LDL) and high-density lipoprotein (HDL), respectively, have “extensive connections” with cardiovascular disease, diabetes, and Alzheimer disease, the authors said.

The apo B/A1 ratio is a known risk index for cardiovascular disease, and in recent studies, it appeared to have some value in prognosis and prediction of gastric and colorectal cancer, among other neoplasms, they added.

In their retrospective study, Dr. Zhang and colleagues analyzed data on 287 metastatic RCC patients who underwent cytoreductive nephrectomy at the Chinese PLA General Hospital. The median age of the patients was 56 years, and the median apo B/A1 ratio was 0.859.

Significantly poorer progression-free survival was seen in the group of patients with a preoperative apo B/A1 ratio over the cutoff of 0.977 (P less than .0001) compared with those under the cutoff, the investigators reported. Likewise, overall survival was poorer for patients with an apo B/A1 ratio over a cutoff of 0.847 (P = .0005).

The apo B/A1 ratio was higher in patients with Fuhrman grade 3-4 versus grade 1-2 patients (P = .010), though the investigators said no significant differences in the ratio were seen in patients stratified by age, body mass index, fatty liver, number of metastases, among other subgroup analyses.

Multivariate analysis revealed that the two independent prognostic factors for progression-free survival were preoperative apo B/A1 ratio and Fuhrman grade, with hazard ratios of 3.131 and 1.906, respectively (P less than .001 for both), while independent prognostic factors for overall survival also included the apo B/A1 ratio (hazard ratio, 2.173; P less than .001) and Fuhrman grade, along with tumor necrosis and receiving targeted therapy.

This retrospective study was limited by relatively small samples from a single center, and the prognostic value of the apo B/A1 ratio needs to be verified in other studies, investigators said.

“Peripheral blood biomarkers only provide a supplement to the traditional prognostic factors in the prediction of the prognosis for patients with metastatic RCC, and are still unable to replace it,” Dr. Zhang and associates said.

The Beijing Natural Science Foundation supported the study. Dr. Zhang and coauthors had no disclosed conflicts of interest related to the work.

SOURCE: Zhang F et al. Urol Oncol. 2018 Nov 30. doi: 10.1016/j.urolonc.2018.11.010.

The ratio of apolipoproteins B and A1 (apo B/A1) is an independent prognostic factor in patients with metastatic renal cell carcinoma, according to authors of a recent retrospective study.

The apo B/A1 ratio, evaluated prior to cytoreductive nephrectomy, was significantly linked with poor progression-free survival and overall survival, according to Fan Zhang, MD, of the Chinese PLA General Hospital in Beijing and coauthors.

Those findings suggest that patients with metastatic RCC should receive “consistent follow-up” that includes evaluation of that ratio, Dr. Zhang and colleagues said.

“As a novel prognostic factor, the preoperative apo B/A1 ratio can be utilized as a supplement to improve the current prognostic evaluation and treatment decision for patients with metastatic RCC,” they wrote in Urologic Oncology.

Apo B and A1, which are predominant components of low-density lipoprotein (LDL) and high-density lipoprotein (HDL), respectively, have “extensive connections” with cardiovascular disease, diabetes, and Alzheimer disease, the authors said.

The apo B/A1 ratio is a known risk index for cardiovascular disease, and in recent studies, it appeared to have some value in prognosis and prediction of gastric and colorectal cancer, among other neoplasms, they added.

In their retrospective study, Dr. Zhang and colleagues analyzed data on 287 metastatic RCC patients who underwent cytoreductive nephrectomy at the Chinese PLA General Hospital. The median age of the patients was 56 years, and the median apo B/A1 ratio was 0.859.

Significantly poorer progression-free survival was seen in the group of patients with a preoperative apo B/A1 ratio over the cutoff of 0.977 (P less than .0001) compared with those under the cutoff, the investigators reported. Likewise, overall survival was poorer for patients with an apo B/A1 ratio over a cutoff of 0.847 (P = .0005).

The apo B/A1 ratio was higher in patients with Fuhrman grade 3-4 versus grade 1-2 patients (P = .010), though the investigators said no significant differences in the ratio were seen in patients stratified by age, body mass index, fatty liver, number of metastases, among other subgroup analyses.

Multivariate analysis revealed that the two independent prognostic factors for progression-free survival were preoperative apo B/A1 ratio and Fuhrman grade, with hazard ratios of 3.131 and 1.906, respectively (P less than .001 for both), while independent prognostic factors for overall survival also included the apo B/A1 ratio (hazard ratio, 2.173; P less than .001) and Fuhrman grade, along with tumor necrosis and receiving targeted therapy.

This retrospective study was limited by relatively small samples from a single center, and the prognostic value of the apo B/A1 ratio needs to be verified in other studies, investigators said.

“Peripheral blood biomarkers only provide a supplement to the traditional prognostic factors in the prediction of the prognosis for patients with metastatic RCC, and are still unable to replace it,” Dr. Zhang and associates said.

The Beijing Natural Science Foundation supported the study. Dr. Zhang and coauthors had no disclosed conflicts of interest related to the work.

SOURCE: Zhang F et al. Urol Oncol. 2018 Nov 30. doi: 10.1016/j.urolonc.2018.11.010.

The ratio of apolipoproteins B and A1 (apo B/A1) is an independent prognostic factor in patients with metastatic renal cell carcinoma, according to authors of a recent retrospective study.

The apo B/A1 ratio, evaluated prior to cytoreductive nephrectomy, was significantly linked with poor progression-free survival and overall survival, according to Fan Zhang, MD, of the Chinese PLA General Hospital in Beijing and coauthors.

Those findings suggest that patients with metastatic RCC should receive “consistent follow-up” that includes evaluation of that ratio, Dr. Zhang and colleagues said.

“As a novel prognostic factor, the preoperative apo B/A1 ratio can be utilized as a supplement to improve the current prognostic evaluation and treatment decision for patients with metastatic RCC,” they wrote in Urologic Oncology.

Apo B and A1, which are predominant components of low-density lipoprotein (LDL) and high-density lipoprotein (HDL), respectively, have “extensive connections” with cardiovascular disease, diabetes, and Alzheimer disease, the authors said.

The apo B/A1 ratio is a known risk index for cardiovascular disease, and in recent studies, it appeared to have some value in prognosis and prediction of gastric and colorectal cancer, among other neoplasms, they added.

In their retrospective study, Dr. Zhang and colleagues analyzed data on 287 metastatic RCC patients who underwent cytoreductive nephrectomy at the Chinese PLA General Hospital. The median age of the patients was 56 years, and the median apo B/A1 ratio was 0.859.

Significantly poorer progression-free survival was seen in the group of patients with a preoperative apo B/A1 ratio over the cutoff of 0.977 (P less than .0001) compared with those under the cutoff, the investigators reported. Likewise, overall survival was poorer for patients with an apo B/A1 ratio over a cutoff of 0.847 (P = .0005).

The apo B/A1 ratio was higher in patients with Fuhrman grade 3-4 versus grade 1-2 patients (P = .010), though the investigators said no significant differences in the ratio were seen in patients stratified by age, body mass index, fatty liver, number of metastases, among other subgroup analyses.

Multivariate analysis revealed that the two independent prognostic factors for progression-free survival were preoperative apo B/A1 ratio and Fuhrman grade, with hazard ratios of 3.131 and 1.906, respectively (P less than .001 for both), while independent prognostic factors for overall survival also included the apo B/A1 ratio (hazard ratio, 2.173; P less than .001) and Fuhrman grade, along with tumor necrosis and receiving targeted therapy.

This retrospective study was limited by relatively small samples from a single center, and the prognostic value of the apo B/A1 ratio needs to be verified in other studies, investigators said.

“Peripheral blood biomarkers only provide a supplement to the traditional prognostic factors in the prediction of the prognosis for patients with metastatic RCC, and are still unable to replace it,” Dr. Zhang and associates said.

The Beijing Natural Science Foundation supported the study. Dr. Zhang and coauthors had no disclosed conflicts of interest related to the work.

SOURCE: Zhang F et al. Urol Oncol. 2018 Nov 30. doi: 10.1016/j.urolonc.2018.11.010.

A review of registry data from a major cancer center revealed a strong, bidirectional association between renal cell carcinoma (RCC) and melanoma.

A greater than twofold risk of melanoma in patients with RCC, and a nearly threefold risk of RCC in melanoma patients, were found in the review of the International Tumor Registry Database at The University of Texas MD Anderson Cancer Center.

The incidence of subsequent melanomas or RCCs in this study was in line with other recent reports from cancer registry analyses, reported Kevin B. Kim, MD, and his coinvestigators.

“Clinicians should be more watchful for these secondary cancers in patients with a history of melanoma or RCC,” they wrote. The report is in Cancer Epidemiology.

They found a total of 13,879 patients with melanoma and 7,597 patients with RCC in their review. Of those patients, 89 had both a melanoma and an RCC diagnosis. About 30% were first diagnosed with RCC, 61% were first diagnosed with melanoma, and 9% had both diagnoses around the same time.

Among the RCC-first patients, the standardized incidence ratio for developing a second primary melanoma was 2.31 (95% confidence interval, 1.52-3.37; P less than .001), while for melanoma-first patients, for developing a second primary RCC, it was 2.87 (95% CI, 2.16-3.74; P less than .001).

Those statistics were consistent with other registry reports, according to Dr. Kim and his colleagues, who wrote that the standardized incidence ratios in those studies ranged from 1.28 to 2.5.

In the MD Anderson registry study, nearly one-third of patients with secondary primary melanoma or RCC had a history of additional secondary cancers, according to the researchers. Those diagnoses included nonmelanoma skin cancers, leukemias, prostate cancer, breast cancer, and colon cancer, among others.

That suggested the presence of possible common risk factors that may have included abnormal genetics, though the database lacked the genetic sequencing and family history data to explore that hypothesis further.

“It would be highly desirable to assess germline genetic information on patients and their families, and also somatic gene aberrations in the tumor lesions, in a more systematic way in order to better elucidate the contribution of the genetics in the association between melanoma and RCC,” Dr. Kim and his colleagues said.

They reported that they had no conflicts of interest.

SOURCE: Kim KB et al. Cancer Epidemiol. 2018 Oct 19;57:80-4.

A review of registry data from a major cancer center revealed a strong, bidirectional association between renal cell carcinoma (RCC) and melanoma.

A greater than twofold risk of melanoma in patients with RCC, and a nearly threefold risk of RCC in melanoma patients, were found in the review of the International Tumor Registry Database at The University of Texas MD Anderson Cancer Center.

The incidence of subsequent melanomas or RCCs in this study was in line with other recent reports from cancer registry analyses, reported Kevin B. Kim, MD, and his coinvestigators.

“Clinicians should be more watchful for these secondary cancers in patients with a history of melanoma or RCC,” they wrote. The report is in Cancer Epidemiology.

They found a total of 13,879 patients with melanoma and 7,597 patients with RCC in their review. Of those patients, 89 had both a melanoma and an RCC diagnosis. About 30% were first diagnosed with RCC, 61% were first diagnosed with melanoma, and 9% had both diagnoses around the same time.

Among the RCC-first patients, the standardized incidence ratio for developing a second primary melanoma was 2.31 (95% confidence interval, 1.52-3.37; P less than .001), while for melanoma-first patients, for developing a second primary RCC, it was 2.87 (95% CI, 2.16-3.74; P less than .001).

Those statistics were consistent with other registry reports, according to Dr. Kim and his colleagues, who wrote that the standardized incidence ratios in those studies ranged from 1.28 to 2.5.

In the MD Anderson registry study, nearly one-third of patients with secondary primary melanoma or RCC had a history of additional secondary cancers, according to the researchers. Those diagnoses included nonmelanoma skin cancers, leukemias, prostate cancer, breast cancer, and colon cancer, among others.

That suggested the presence of possible common risk factors that may have included abnormal genetics, though the database lacked the genetic sequencing and family history data to explore that hypothesis further.

“It would be highly desirable to assess germline genetic information on patients and their families, and also somatic gene aberrations in the tumor lesions, in a more systematic way in order to better elucidate the contribution of the genetics in the association between melanoma and RCC,” Dr. Kim and his colleagues said.

They reported that they had no conflicts of interest.

SOURCE: Kim KB et al. Cancer Epidemiol. 2018 Oct 19;57:80-4.

A review of registry data from a major cancer center revealed a strong, bidirectional association between renal cell carcinoma (RCC) and melanoma.

A greater than twofold risk of melanoma in patients with RCC, and a nearly threefold risk of RCC in melanoma patients, were found in the review of the International Tumor Registry Database at The University of Texas MD Anderson Cancer Center.

The incidence of subsequent melanomas or RCCs in this study was in line with other recent reports from cancer registry analyses, reported Kevin B. Kim, MD, and his coinvestigators.

“Clinicians should be more watchful for these secondary cancers in patients with a history of melanoma or RCC,” they wrote. The report is in Cancer Epidemiology.

They found a total of 13,879 patients with melanoma and 7,597 patients with RCC in their review. Of those patients, 89 had both a melanoma and an RCC diagnosis. About 30% were first diagnosed with RCC, 61% were first diagnosed with melanoma, and 9% had both diagnoses around the same time.

Among the RCC-first patients, the standardized incidence ratio for developing a second primary melanoma was 2.31 (95% confidence interval, 1.52-3.37; P less than .001), while for melanoma-first patients, for developing a second primary RCC, it was 2.87 (95% CI, 2.16-3.74; P less than .001).

Those statistics were consistent with other registry reports, according to Dr. Kim and his colleagues, who wrote that the standardized incidence ratios in those studies ranged from 1.28 to 2.5.

In the MD Anderson registry study, nearly one-third of patients with secondary primary melanoma or RCC had a history of additional secondary cancers, according to the researchers. Those diagnoses included nonmelanoma skin cancers, leukemias, prostate cancer, breast cancer, and colon cancer, among others.

That suggested the presence of possible common risk factors that may have included abnormal genetics, though the database lacked the genetic sequencing and family history data to explore that hypothesis further.

“It would be highly desirable to assess germline genetic information on patients and their families, and also somatic gene aberrations in the tumor lesions, in a more systematic way in order to better elucidate the contribution of the genetics in the association between melanoma and RCC,” Dr. Kim and his colleagues said.

They reported that they had no conflicts of interest.

SOURCE: Kim KB et al. Cancer Epidemiol. 2018 Oct 19;57:80-4.

© ASH/Luke Franke 2018

SAN DIEGO—Emapalumab, an interferon gamma-blocking antibody, controls disease activity and has a favorable safety profile in pediatric patients with primary hemophagocytic lymphohistiocytosis (HLH), according to research presented at the 2018 ASH Annual Meeting.

Investigators believe emapalumab, which was recently approved to treat HLH in the United States, should be considered a new therapeutic option for this rare and life-threatening syndrome because of the drug’s targeted mode of action.

Multiple lines of evidence have pointed to interferon gamma as a “rational target” in HLH, and elevated levels of interferon gamma are consistently observed in patients with HLH, said Franco Locatelli, MD, of Ospedale Pediatrico Bambino Gesù in Rome, Italy.

Emapalumab binds to its target with high affinity, recognizing both free and receptor-bound interferon gamma, he added.

Dr. Locatelli described trial results with emapalumab in children with HLH during the late-breaking abstracts session at ASH (abstract LBA-6).

This phase 2/3 study (NCT01818492) included 34 children with primary HLH—7 who were treatment-naïve and 27 who had failed conventional HLH therapy.

The patients received emapalumab intravenously with concomitant dexamethasone for up to 8 weeks or extended to the point of allogeneic hematopoietic stem cell transplant if needed.

The study met its primary endpoint of overall response rate higher than 40%, Dr. Locatelli reported.

The overall response rate was 64.7% for all 34 treated patients (95% confidence interval [CI], 46% to 80%; P=0.0031) and 63% for the 27 patients who had failed prior therapy (95% CI, 42% to 81%; P=0.0134).

Response was rapid, occurring at a median of 8 days after starting emapalumab, and patients were in response for a median of 75% of days during treatment, Dr. Locatelli said.

Ninety-four percent of patients had at least one adverse event (AE), and 63% had serious AEs. Common AEs included infections (56%), hypertension (35%), infusion-related reactions (27%), and pyrexia (24%).

One patient had disseminated histoplasmosis that led to discontinuation of emapalumab but resolved with appropriate treatment.

This study was sponsored by Novimmune. Investigators provided disclosures related to Sobi, Novimmune, Rocket Pharmaceuticals, Inc., AB2Bio, Novartis, Eli Lilly, Sanofi, UCB, Pfizer, and AbbVie. Two investigators reported employment with Novimmune.

© ASH/Luke Franke 2018

SAN DIEGO—Emapalumab, an interferon gamma-blocking antibody, controls disease activity and has a favorable safety profile in pediatric patients with primary hemophagocytic lymphohistiocytosis (HLH), according to research presented at the 2018 ASH Annual Meeting.

Investigators believe emapalumab, which was recently approved to treat HLH in the United States, should be considered a new therapeutic option for this rare and life-threatening syndrome because of the drug’s targeted mode of action.

Multiple lines of evidence have pointed to interferon gamma as a “rational target” in HLH, and elevated levels of interferon gamma are consistently observed in patients with HLH, said Franco Locatelli, MD, of Ospedale Pediatrico Bambino Gesù in Rome, Italy.

Emapalumab binds to its target with high affinity, recognizing both free and receptor-bound interferon gamma, he added.

Dr. Locatelli described trial results with emapalumab in children with HLH during the late-breaking abstracts session at ASH (abstract LBA-6).

This phase 2/3 study (NCT01818492) included 34 children with primary HLH—7 who were treatment-naïve and 27 who had failed conventional HLH therapy.

The patients received emapalumab intravenously with concomitant dexamethasone for up to 8 weeks or extended to the point of allogeneic hematopoietic stem cell transplant if needed.

The study met its primary endpoint of overall response rate higher than 40%, Dr. Locatelli reported.

The overall response rate was 64.7% for all 34 treated patients (95% confidence interval [CI], 46% to 80%; P=0.0031) and 63% for the 27 patients who had failed prior therapy (95% CI, 42% to 81%; P=0.0134).

Response was rapid, occurring at a median of 8 days after starting emapalumab, and patients were in response for a median of 75% of days during treatment, Dr. Locatelli said.

Ninety-four percent of patients had at least one adverse event (AE), and 63% had serious AEs. Common AEs included infections (56%), hypertension (35%), infusion-related reactions (27%), and pyrexia (24%).

One patient had disseminated histoplasmosis that led to discontinuation of emapalumab but resolved with appropriate treatment.

This study was sponsored by Novimmune. Investigators provided disclosures related to Sobi, Novimmune, Rocket Pharmaceuticals, Inc., AB2Bio, Novartis, Eli Lilly, Sanofi, UCB, Pfizer, and AbbVie. Two investigators reported employment with Novimmune.

© ASH/Luke Franke 2018

SAN DIEGO—Emapalumab, an interferon gamma-blocking antibody, controls disease activity and has a favorable safety profile in pediatric patients with primary hemophagocytic lymphohistiocytosis (HLH), according to research presented at the 2018 ASH Annual Meeting.

Investigators believe emapalumab, which was recently approved to treat HLH in the United States, should be considered a new therapeutic option for this rare and life-threatening syndrome because of the drug’s targeted mode of action.

Multiple lines of evidence have pointed to interferon gamma as a “rational target” in HLH, and elevated levels of interferon gamma are consistently observed in patients with HLH, said Franco Locatelli, MD, of Ospedale Pediatrico Bambino Gesù in Rome, Italy.

Emapalumab binds to its target with high affinity, recognizing both free and receptor-bound interferon gamma, he added.

Dr. Locatelli described trial results with emapalumab in children with HLH during the late-breaking abstracts session at ASH (abstract LBA-6).

This phase 2/3 study (NCT01818492) included 34 children with primary HLH—7 who were treatment-naïve and 27 who had failed conventional HLH therapy.

The patients received emapalumab intravenously with concomitant dexamethasone for up to 8 weeks or extended to the point of allogeneic hematopoietic stem cell transplant if needed.

The study met its primary endpoint of overall response rate higher than 40%, Dr. Locatelli reported.

The overall response rate was 64.7% for all 34 treated patients (95% confidence interval [CI], 46% to 80%; P=0.0031) and 63% for the 27 patients who had failed prior therapy (95% CI, 42% to 81%; P=0.0134).

Response was rapid, occurring at a median of 8 days after starting emapalumab, and patients were in response for a median of 75% of days during treatment, Dr. Locatelli said.

Ninety-four percent of patients had at least one adverse event (AE), and 63% had serious AEs. Common AEs included infections (56%), hypertension (35%), infusion-related reactions (27%), and pyrexia (24%).

One patient had disseminated histoplasmosis that led to discontinuation of emapalumab but resolved with appropriate treatment.

This study was sponsored by Novimmune. Investigators provided disclosures related to Sobi, Novimmune, Rocket Pharmaceuticals, Inc., AB2Bio, Novartis, Eli Lilly, Sanofi, UCB, Pfizer, and AbbVie. Two investigators reported employment with Novimmune.

SAN DIEGO – An inexpensive, rapid, and easy-to-use blood test was more than 99% accurate in detecting sickle cell disease in young children in sub-Saharan Africa, according to research reported at the annual meeting of the American Society of Hematology.

Courtesy American Society of Hematology

The test, called HemoTypeSC, uses monoclonal antibodies to detect hemoglobins A, S, and C in a drop of whole blood, said investigator Erik Serrao, PhD, of Silver Lake Research in Azusa, Calif.

Findings from the diagnostic accuracy trial, which included 1,000 children in Uganda, suggest that the immunoassay is a promising tool to enable newborn and general population screening in resource-constrained regions of high prevalence, such as Africa and India.

“Early screening plus treatment plus counseling equals saving millions of lives over the coming decades, and we believe HemoTypeSC can form an integral part of the initial part of this equation,” Dr. Serrao said during a late-breaking abstract session at the meeting.

Each test kit costs less than $2 to the end user; requires no electricity, special equipment, or training; and delivers results in about 10 minutes, he added.


Of all the late-breaking abstracts at ASH this year, the study by Dr. Serrao and his colleagues is the one with the potential to save the most lives, said Mark Crowther, MD, of McMaster University, Hamilton, Ont.

“The ability to diagnose sickle cell disease early and intervene early will result in potentially thousands of infants, who would otherwise die in infancy or early childhood, surviving into adulthood,” Dr. Crowther said during a press briefing.

Using current gold standard methods for diagnosing sickle cell disease is, at minimum, challenging and “frankly impossible” in many low-resource settings, because of the cost and the requirement for sophisticated equipment and reliable electricity, Dr. Crowther added.

In the study, investigators compared results of the HemoTypeSC test with hemoglobin electrophoresis for detection of the phenotypes HbAA (normal), HbAS (sickle cell trait), and HbSS (sickle cell disease). They compared these two testing methods in 1,000 children between the ages of 1 month and 5 years who were prospectively recruited from hospital wards and outpatient clinics in Uganda.

The immunoassay had an overall accuracy of 99.8%, correctly identifying 998 of 1,000 phenotypes as initially determined by electrophoresis. Specifically, the test correctly identified 100% of the 720 HbAA specimens, 100% of 182 HbAS specimens, and 98% of HbSS, or 96 of 98 specimens, leaving just 2 discordant samples, both of which HemoTypeSC identified as HbAS.

Investigators subsequently discovered that both of the individuals with the discordant samples had previously been diagnosed with sickle cell disease and had received recent transfusions. Both cases were subsequently confirmed as HbSS in review of previous diagnostic result reports, bringing the accuracy rate up to 100% in a secondary analysis also reported at the meeting.

Although this particular study excluded newborns, a different study of the immunoassay, recently published in the American Journal of Hematology, demonstrated 100% accuracy across multiple phenotypes in the setting of newborn screening (2018 Oct 5. doi: 10.1002/ajh.25305).

Sickle cell disease screening programs have been projected to be cost effective in Africa, Dr. Serrano said, and could even save money for governments over time as budgets are reallocated toward screening, with less money needed for treatment of patients presenting with severe complications in hospitals.

Dr. Serrao reported that he is an employee of Silver Lake Research, which funded the study, approved the study design, and donated HemoTypeSC tests.

On March 11, 2019, the editors of Blood, an ASH journal, retracted the abstract for this study. The second listed author on the abstract said that it was submitted without his consent or approval. The retraction makes no statement on the underlying science of the study, the editors noted.

This article was updated on 3/14/2019.

SOURCE: Serrao E et al. ASH 2018, Abstract LBA-3.

SAN DIEGO – An inexpensive, rapid, and easy-to-use blood test was more than 99% accurate in detecting sickle cell disease in young children in sub-Saharan Africa, according to research reported at the annual meeting of the American Society of Hematology.

Courtesy American Society of Hematology

The test, called HemoTypeSC, uses monoclonal antibodies to detect hemoglobins A, S, and C in a drop of whole blood, said investigator Erik Serrao, PhD, of Silver Lake Research in Azusa, Calif.

Findings from the diagnostic accuracy trial, which included 1,000 children in Uganda, suggest that the immunoassay is a promising tool to enable newborn and general population screening in resource-constrained regions of high prevalence, such as Africa and India.

“Early screening plus treatment plus counseling equals saving millions of lives over the coming decades, and we believe HemoTypeSC can form an integral part of the initial part of this equation,” Dr. Serrao said during a late-breaking abstract session at the meeting.

Each test kit costs less than $2 to the end user; requires no electricity, special equipment, or training; and delivers results in about 10 minutes, he added.


Of all the late-breaking abstracts at ASH this year, the study by Dr. Serrao and his colleagues is the one with the potential to save the most lives, said Mark Crowther, MD, of McMaster University, Hamilton, Ont.

“The ability to diagnose sickle cell disease early and intervene early will result in potentially thousands of infants, who would otherwise die in infancy or early childhood, surviving into adulthood,” Dr. Crowther said during a press briefing.

Using current gold standard methods for diagnosing sickle cell disease is, at minimum, challenging and “frankly impossible” in many low-resource settings, because of the cost and the requirement for sophisticated equipment and reliable electricity, Dr. Crowther added.

In the study, investigators compared results of the HemoTypeSC test with hemoglobin electrophoresis for detection of the phenotypes HbAA (normal), HbAS (sickle cell trait), and HbSS (sickle cell disease). They compared these two testing methods in 1,000 children between the ages of 1 month and 5 years who were prospectively recruited from hospital wards and outpatient clinics in Uganda.

The immunoassay had an overall accuracy of 99.8%, correctly identifying 998 of 1,000 phenotypes as initially determined by electrophoresis. Specifically, the test correctly identified 100% of the 720 HbAA specimens, 100% of 182 HbAS specimens, and 98% of HbSS, or 96 of 98 specimens, leaving just 2 discordant samples, both of which HemoTypeSC identified as HbAS.

Investigators subsequently discovered that both of the individuals with the discordant samples had previously been diagnosed with sickle cell disease and had received recent transfusions. Both cases were subsequently confirmed as HbSS in review of previous diagnostic result reports, bringing the accuracy rate up to 100% in a secondary analysis also reported at the meeting.

Although this particular study excluded newborns, a different study of the immunoassay, recently published in the American Journal of Hematology, demonstrated 100% accuracy across multiple phenotypes in the setting of newborn screening (2018 Oct 5. doi: 10.1002/ajh.25305).

Sickle cell disease screening programs have been projected to be cost effective in Africa, Dr. Serrano said, and could even save money for governments over time as budgets are reallocated toward screening, with less money needed for treatment of patients presenting with severe complications in hospitals.

Dr. Serrao reported that he is an employee of Silver Lake Research, which funded the study, approved the study design, and donated HemoTypeSC tests.

On March 11, 2019, the editors of Blood, an ASH journal, retracted the abstract for this study. The second listed author on the abstract said that it was submitted without his consent or approval. The retraction makes no statement on the underlying science of the study, the editors noted.

This article was updated on 3/14/2019.

SOURCE: Serrao E et al. ASH 2018, Abstract LBA-3.

SAN DIEGO – An inexpensive, rapid, and easy-to-use blood test was more than 99% accurate in detecting sickle cell disease in young children in sub-Saharan Africa, according to research reported at the annual meeting of the American Society of Hematology.

Courtesy American Society of Hematology

The test, called HemoTypeSC, uses monoclonal antibodies to detect hemoglobins A, S, and C in a drop of whole blood, said investigator Erik Serrao, PhD, of Silver Lake Research in Azusa, Calif.

Findings from the diagnostic accuracy trial, which included 1,000 children in Uganda, suggest that the immunoassay is a promising tool to enable newborn and general population screening in resource-constrained regions of high prevalence, such as Africa and India.

“Early screening plus treatment plus counseling equals saving millions of lives over the coming decades, and we believe HemoTypeSC can form an integral part of the initial part of this equation,” Dr. Serrao said during a late-breaking abstract session at the meeting.

Each test kit costs less than $2 to the end user; requires no electricity, special equipment, or training; and delivers results in about 10 minutes, he added.


Of all the late-breaking abstracts at ASH this year, the study by Dr. Serrao and his colleagues is the one with the potential to save the most lives, said Mark Crowther, MD, of McMaster University, Hamilton, Ont.

“The ability to diagnose sickle cell disease early and intervene early will result in potentially thousands of infants, who would otherwise die in infancy or early childhood, surviving into adulthood,” Dr. Crowther said during a press briefing.

Using current gold standard methods for diagnosing sickle cell disease is, at minimum, challenging and “frankly impossible” in many low-resource settings, because of the cost and the requirement for sophisticated equipment and reliable electricity, Dr. Crowther added.

In the study, investigators compared results of the HemoTypeSC test with hemoglobin electrophoresis for detection of the phenotypes HbAA (normal), HbAS (sickle cell trait), and HbSS (sickle cell disease). They compared these two testing methods in 1,000 children between the ages of 1 month and 5 years who were prospectively recruited from hospital wards and outpatient clinics in Uganda.

The immunoassay had an overall accuracy of 99.8%, correctly identifying 998 of 1,000 phenotypes as initially determined by electrophoresis. Specifically, the test correctly identified 100% of the 720 HbAA specimens, 100% of 182 HbAS specimens, and 98% of HbSS, or 96 of 98 specimens, leaving just 2 discordant samples, both of which HemoTypeSC identified as HbAS.

Investigators subsequently discovered that both of the individuals with the discordant samples had previously been diagnosed with sickle cell disease and had received recent transfusions. Both cases were subsequently confirmed as HbSS in review of previous diagnostic result reports, bringing the accuracy rate up to 100% in a secondary analysis also reported at the meeting.

Although this particular study excluded newborns, a different study of the immunoassay, recently published in the American Journal of Hematology, demonstrated 100% accuracy across multiple phenotypes in the setting of newborn screening (2018 Oct 5. doi: 10.1002/ajh.25305).

Sickle cell disease screening programs have been projected to be cost effective in Africa, Dr. Serrano said, and could even save money for governments over time as budgets are reallocated toward screening, with less money needed for treatment of patients presenting with severe complications in hospitals.

Dr. Serrao reported that he is an employee of Silver Lake Research, which funded the study, approved the study design, and donated HemoTypeSC tests.

On March 11, 2019, the editors of Blood, an ASH journal, retracted the abstract for this study. The second listed author on the abstract said that it was submitted without his consent or approval. The retraction makes no statement on the underlying science of the study, the editors noted.

This article was updated on 3/14/2019.

SOURCE: Serrao E et al. ASH 2018, Abstract LBA-3.